Palmitoylation in Crohn’s disease: Current status and future directions

Abstract

S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn’s disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.

Integrating the analysis of human biopsies using post‐translational modifications proteomics

“…This collection of palmitoylated proteins is referred to as the “palmitoylome,” and >600 substrates have been identified and characterized so far (Jin et al, 2021 ). Various techniques have been used to detect S‐palmitoylation including acyl‐biotin exchange (ABE), acyl‐resin‐assisted capture (Acyl‐Rac), and acyl‐PEG exchange (APE) followed by LC–MS/MS (Cheng et al, 2021 ; Jeong et al, 2023 ; Ji et al, 2013 ). The dysregulation of protein S‐palmitoylation has been linked to the development of various human diseases, including viral infections, cancer, diabetes, as well as immunological and neurological disorders.…”

S‐palmitoylation regulates innate immune signaling pathways: molecular mechanisms and targeted therapies

“…Dextran sulfate sodium-induced colitis in mice is reduced by treatment with the APT2 inhibitor ML349 and Zdhhc7 knockout [121]. Therefore, the STAT3 S-palmitoylation/de-palmitoylation cycle could be a target for Th17-related immune disorders, suggesting that inhibition of STAT3 S-palmitoylation/de-palmitoylation can be a potential therapeutic strategy for IBD [121,155].…”

“…Environmental influences, genetic factors, and abnormal infections often contribute to inducing AIDs. Multiple studies have indicated that NOD1 and NOD2 polymorphisms are involved in a variety of AIDs, including Crohn's disease, Blau syndrome, Behcet's syndrome, atopic diseases, and early-onset sarcoidosis [155][156][157]. CD-associated NOD2-loss-of-function variants with reduced Spalmitoylation levels lead to less NOD2-membrane association and are incapable of NOD2 signaling, while the increased Spalmitoylation of early-onset sarcoidosis-or BS-associated NOD2 gain-of-function mutants drives NF-κB hyperactivity [112,158].…”

Potential roles of enteric glial cells in Crohn's disease: A critical review

“…Numerous pro‐inflammatory genes that encode cytokines, chemokines, and adhesion molecules crucial for inflammation and immunological responses are stimulated by NF‐κB 132 . The NF‐κB signalling pathway regulates the expression of TNF‐α, IL‐1, IL‐6, IL‐12, IL‐23, and IκBa 133 . Anti‐TNF antibodies, including infliximab, adalimumab, and certolizumab, 134–136 are a first‐line treatment for CD and several other autoimmune illnesses 137 .…”

“…Anti‐TNF antibodies, including infliximab, adalimumab, and certolizumab, 134–136 are a first‐line treatment for CD and several other autoimmune illnesses 137 . Other biologic medications include IL‐12/23 antibodies, e.g., ustekinumab, 138 and corticosteroids, which exert immunosuppressive effects by increasing IκBα, a crucial component of the NF‐κB pathway 133 . In addition to immunomodulatory effects, anti‐TNF therapy could increase IL‐22 production in patients with CD and consequently promote intestinal epithelial barrier restoration 139 .…”